Expression of p53 protein correlates with decreased survival in patients with areca quid chewing and smoking-associated oral squamous cell carcinomas in Taiwan

Expression of p53 protein was examined in oral squamous cell carcinoma (SCC) from patients who were areca quid (AQ) chewers and/or tobacco smokers, using anti-p53 antibodies with an immunoperoxidase technique. Positive p53 stain was observed in 47 of 81 (58%) cases of oral SCC. p53 overexpression was found to higher in patients without AQ chewing and smoking habits than in patients with these two habits (80% vs 52%, P=0.076). No significant correlation was found between p53 expression and the patients' age, sex, cancer location, clinical staging, primary tumor TNM status, or histological differentiation of SCC. The Kaplan-Meier analysis showed that the prognosis for patients with p53-negative tumors was significantly better than that for patients with p53-positive tumors (P<0.05). A significant correlation was also observed between positive lymph node status and poor prognosis (P<0.05). These results suggest that p53 may serve as an adjuvant marker of poor survival in patients with oral SCCs in Taiwan.     

Expression of phosphorylated Akt in oral carcinogenesis and its induction by nicotine and alkaline stimulation

Background:  In Taiwan, it is well documented that cigarette smoking and areca nut chewing contribute to the risk of oral squamous cell carcinoma (OSCC). The role of phosphorylated Akt (p-Akt) in oral carcinogenesis induced by nicotine and alkaline environments was investigated.
Method:  Immunohistochemistry (IHC) was used to detect p-Akt expression in cancerous ( n  = 30) precancerous ( n  = 30), and normal mucosa tissues ( n  = 10). Western blotting was used to detect time-dependent induction of p-Akt by 100 μM nicotine in normal human bronchial epithelial cell (NHBE), normal human oral keratinocytes (NHOK), immortalized human epithelial cells (HaCaT) and OEC-M1 cells, dose-dependent induction of p-Akt in OEC-M1 and HaCaT cells and pH effect of p-Akt in OEC-M1. The unpaired t -test and the Fisher's exact test were used to analyze the p-Akt immunoreactivity in various groups and its association with clinicopathological parameters.
Results:  Higher p-Akt expression in cancerous group than in normal mucosa ( P  = 0.0002) and precancerous ( P  = 0.0049) groups was observed. A time-dependent increase in p-Akt in the NHBE, NHOK, HaCaT and OEC-M1 cell lines was observed with 100 μM nicotine treatment. The dose-dependent increase in p-Akt by nicotine treatment in HaCaT and OEC-M1 cells was obviously observed. Higher p-Akt expression in more alkaline environment (pH 8.0) was observed than at pH 7.4 in OEC-M1 cells.
Conclusion:  A potential role for increased p-Akt may relate to the dose and time of nicotine use. The potential role of an alkaline environment to enhance nicotine-related oral carcinogenesis may exist.     

民族药儿茶的生药学鉴定

目的 对多民族常用的植物药儿茶进行生药学鉴定,为其鉴别及应用提供科学依据.方法 采用原植物、性状、显微和薄层鉴别的方法 .结果 儿茶在原植物、性状、显微和薄层等方面具有专属性的特征.结论 通过原植物、性状、显微鉴别和薄层能够很好地鉴定该药材.     

A Positive Relationship between Betel Nut Chewing and Significant Liver Fibrosis in NAFLD Subjects,but Not in Non-NAFLD Ones

Background: Betel nut chewing is associated with oral cancer, cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma (HCC). The aim of this study was to explore the association of betel nut chewing with liver fibrosis in subjects with and without nonalcoholic fatty liver disease (NAFLD). Method: A total of 5967 subjects were enrolled. NAFLD was diagnosed with ultrasonography. Betel nut chewing was classified into non-chewing, ex-chewing, and current chewing, and cumulative dosages were calculated. The aspartate aminotransferase (AST)/platelet ratio index and NAFLD fibrosis scores (NFS) were calculated for evaluation of liver fibrosis. Results: NAFLD increased the associated risk of liver fibrosis in those with (odds ratio (OR): 5.51, 95% confidence interval (CI): 3.09–9.80) and without betel nut chewing (OR: 2.33, 95% CI: 1.64–3.29). In subjects without NAFLD, betel nut chewing was not associated with liver fibrosis (OR: 1.12, 95% CI: 0.44–2.86). In subjects with NAFLD, cumulative betel nut chewing and ex- and current chewing were positively associated with NFS and significant liver fibrosis. Conclusions: In subjects with NAFLD, betel nut chewing, even ex-chewing, was associated with a higher risk of liver fibrosis, where higher cumulative levels were found to increase the risk of significant liver fibrosis. However, the associated risk of liver fibrosis due to betel nut chewing was insignificant in subjects without NAFLD.     

槟榔致癌物质与口腔癌

槟榔为一级致癌物,咀嚼槟榔引起口腔癌缘于槟榔中的槟榔碱（ARC）、槟榔鞣质、槟榔特异性亚硝胺（ASNA）和活性氧（ROS）等具有细胞毒性、遗传毒性、致突变性和致癌性。ARC可诱导口腔成纤维细胞、角质形成细胞和人脐静脉内皮细胞程序性死亡。槟榔鞣质有否遗传毒性和致突变性至今仍有争议,不同类型的短期筛选试验结果差异很大,但含鞣质的槟榔多酚是槟榔的主要致癌成分。3-甲基亚硝氨基内醛可诱发人颊黏膜角质形成细胞的DNA链断裂和DNA蛋白交联。3-甲基亚硝氨基丙腈为强致癌剂,可诱发试验动物肿瘤,靶器官包括鼻腔、食管、舌等。槟榔咀嚼过程中可产生大量的ROS,造成DNA氧化性损伤和激活癌基因的方式促使癌症的发生。相对分子质量为3．0×10^4-10．0×10^4的槟榔提取物组分中一种新发现的蛋白聚糖通过增加胞内ROS水平及一系列信号级联放大,上调口腔癌细胞低氧诱导因子-1d的表达,最终诱导细胞自噬。细胞自噬有利于保护癌细胞免遭ARC诱导的程序性细胞死亡,促进口腔癌的发展。槟榔提取物还可能通过ROS增强舌鳞状上皮细胞癌细胞株刺激血小板聚集的效应,从而促进舌癌转移。     

Effect of betel chewing, tobacco smoking and alcohol consumption on oral submucous fibrosis: a case–control study in Sri Lanka

BACKGROUND: Oral submucous fibrosis (OSMF) is a chronic, insidious, disabling potentially malignant condition of the oral mucosa seen predominantly in south and Southeast Asia. No reports are hitherto available on the aetiological factors of OSMF based on Sri Lankan patients. METHODS: A total of 74 patients with OSMF and 74 controls who consecutively attended the Oral Medicine clinic at the Dental Hospital (Teaching) Faculty of Dental Sciences, University of Peradeniya, Sri Lanka were included in the study. Binary logistic regression analyses were performed to model the influence of betel chewing, smoking and alcohol use and to determine the effects of different combinations of chewing habits on OSMF. RESULTS: Betel chewing was the only significantly associated factor in the aetiology of OSMF (OR = 171.83, 95% CI: 36.35-812.25). There were no interaction effects of chewing, smoking and alcohol consumption in the causation of OSMF. CONCLUSION: The present study has shown a strong association of betel quid chewing (including tobacco as an ingredient) with the causation of OSMF.     

Development of an in vivo mouse model to study oral submucous fibrosis

BACKGROUND: Epidemiological data have shown an association of areca nut chewing with oral submucous fibrosis (OSF). Experimental evidence to confirm this has been limited. Fibrosis-promoting activity of areca nut was tested in an animal model. METHOD: Buccal mucosa of a group of 20 female BALB/c strain mice, 10-12 weeks of age, was treated twice daily 6 days per week with topical application of aqueous areca nut extracts for 300-600 days. A control group (n = 20) was treated with 50 mM NaCl. The influence of areca nut on the oral epithelium and connective tissue was recorded semiquantitatively by light microscopy. RESULTS: The areca nut-treated oral epithelium showed progressive changes in epithelial thickness leading to atrophy, increased cellularity of fibroblasts, fibrosis of connective tissue, focal infiltration of inflammatory cells and muscle atrophy. On killing after 600 days of treatment, the scores on cellularity, inflammation and muscle atrophy were significantly different to the control group (P = 0.03). CONCLUSION: The study provides further evidence that areca nut contributes to the development of OSF in treated animals. The model has the potential to test synergism of areca nut with other carcinogens and any therapeutic interventions.     

黔园九号芦笋对环磷酰胺所致大鼠骨髓抑制的保护作用

研究口服芦笋干粉对腹腔注射环磷酰胺造成大鼠骨髓抑制的影响。结果表明环磷酰胺注射５天后芦笋组大鼠外周血白、红细胞数的减少明显轻于对照组，注射十天后芦笋组骨髓有核细胞增生活跃，外周血白、红细胞数量的回升也明显快于对照组。本研究表明芦笋对环磷酰胺造成的骨髓抑制有保护作用。     

Prognostic role of p21WAF1 expression in areca quid chewing and smoking-associated oral squamous cell carcinoma in Taiwan.

BACKGROUND: Alterations in p21WAF1 protein expression have been observed in a wide variety of human cancers by immunohistochemistry, and both decreased and increased levels of p21WAF1 protein expression have been shown to correlate with poor prognosis. METHOD: To examine the relation between p21WAF1 protein expression and prognosis in oral squamous cell carcinomas (SCCs), we performed an immunohistochemical study with antip21WAF1 antibody on 43 oral SCCs. Immunostaining results were then correlated with p53 protein levels, clinicopathological parameters of the tumors and overall patient survival. RESULTS: Of the 43 patients, 31 (72%) had tumors with positive p21WAF1 nuclear staining and 27 (63%) had tumors with p53 nuclear staining. There was no significant correlation between p21WAF1 and p53 protein expressions and both mutant p53-containing oral SCCs overexpressed p21WAF1 protein. In addition, no significant correlation was found between the p21WAF1 expression and the patients' age, sex, oral habit, cancer location, or primary tumor TNM status at the time of initial presentation. The Kaplan-Meier analysis showed a significant correlation between p21WAF1 protein overexpression and poor patient overall survival (P = 0.049). When p53 and p21WAF1 were evaluated together, the 5-year overall survival was lowest in p53(+)-p21WAF1(+) patients and highest in p53(-)-p21WAF1(-) patients (P = 0.057). CONCLUSION: Combined evaluation of p21WAF1 and p53 expressions may be useful in estimating the prognosis of patients with oral SCCs in Taiwan.